Polymorphisms in the DNA repair gene XRCC1 and age-related disease

Mech Ageing Dev. 2003 Jan;124(1):27-32. doi: 10.1016/s0047-6374(02)00166-5.


The recent hypothesis that common variants (single nucleotide polymorphisms or SNPs) in the population may contribute significantly to genetic risk for common diseases permits a conceptually straightforward approach to identifying age-related disease-causing mutations. Functional variants of DNA replication and repair genes might be expected to be highly significant to cancer and aging since replication must proceed with high fidelity in a cellular environment where an estimated 10000 nucleotides are damaged daily. Single-strand breaks (SSB) are one of the results of DNA damage either by methylation, oxidation, reduction or fragmentation of bases by ionizing radiation, and arise in cells directly by disintegration of damaged sugars or indirectly as intermediates of base excision repair. Studies have demonstrated a role for XRCC1 both in vitro and in vivo during the repair of SSB. A number of SNPs have been identified for the XRCC1 gene, and several have been associated with age-related diseases, especially cancer. This report provides resequencing data confirming the existence of commonly occurring SNPs, including Arg194Trp and Arg399Gln, and briefly summarizes epidemiological and functional relevance to cancer and other age-related diseases. XRCC1 SNPs will be useful probes for investigating age-associated pathobiology in epidemiological and mechanistic studies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / genetics
  • Breast Neoplasms / genetics
  • Case-Control Studies
  • DNA Damage
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Lung Neoplasms / genetics
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Skin Neoplasms / genetics
  • X-ray Repair Cross Complementing Protein 1


  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Xrcc1 protein, mouse